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Correspondence |

Ciliary Beat Pattern Analysis Below 37°C May Increase Risk of Primary Ciliary Dyskinesia MisdiagnosisMisdiagnosis Risk for Primary Ciliary Dyskinesia FREE TO VIEW

Claire L. Jackson, PhD; Patricia M. Goggin, MMedSci; Jane S. Lucas, PhD; for the Genetic Disorders of Mucociliary Clearance Consortium
Author and Funding Information

From the Primary Ciliary Dyskinesia Diagnostic Service, University Hospital Southampton Foundation Trust; and Primary Ciliary Dyskinesia Research Group, Clinical and Experimental Sciences, Southampton National Institute for Health Research, Respiratory Biomedical Research Unit Faculty of Medicine, University of Southampton.

Correspondence to: Jane S Lucas, PhD, Primary Ciliary Dyskinesia Diagnostic Service, Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, Mailpoint 803, University Hospital Southampton Foundation Trust, Tremona Rd, Southampton, SO16 6YD, England; e-mail: jlucas1@soton.ac.uk


Funding/Support: The National Diagnostic PCD service in Southampton is funded by the National Specialised Commissioning Team.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2012;142(2):543-544. doi:10.1378/chest.11-3253
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Published online

We read with interest the article by Smith et al1 published in CHEST (July 2011). The authors analyzed ciliary function in 14 nasal turbinate brushing biopsy specimens that provided ciliated epithelium from healthy human volunteers. The authors stated that ciliary function was maintained at temperatures ranging between 37°C and 2°C, contrary to previous research suggesting that cilia stop beating at 4°C,2-4 and a sigmoid relationship between ciliary beat frequency (CBF) and temperature was observed. The authors suggested that a normal ciliary beat pattern (CBP) may be analyzed at temperatures as low as 2°C and that cooling of cilia may allow interrogation of CBP for diagnostic testing without the need for expensive, high-speed video microscopy. We are in agreement that additional CBP analysis is invaluable over CBF alone for the diagnosis of primary ciliary dyskinesia (PCD), particularly for those with normal CBF ranges. However, it is important to highlight that assessing CBP at temperatures below 37°C may increase the likelihood of misdiagnosis.

We were recently referred an 8-month-old girl with a strong clinical history of PCD (respiratory and nasal symptoms since birth, situs inversus, and serous otitis media). Using high-speed video microscopy we recorded abnormal and hyperfrequent ciliary function at 37°C on four separate occasions, despite normal ciliary ultrastructure consistent with atypical PCD.5,6 On two occasions the CBF and CBP were assessed at 37°C and room temperatures (measured at 21°C-24°C). CBF from at least six separate ciliated cell clusters measured at 37°C was hyperfrequent on both occasions (mean, 26.3 Hz [SD ±3.4]; 34.4 Hz [SD ±13.5]). However, when measured at room temperature, the CBF measurements were within normal range (11-18 Hz) (mean, 12.6 Hz [SD ±0.8]; 15.2 Hz [SD ±4.5]). CBP at 37°C was consistently abnormal, with interrupted, dyskinetic, hyperfrequent ciliary beating, and cilia lacked the normal range of motion (Video 1). Cilia were directly compared on the same epithelial edge at 37°C and room temperature, and, as described previously, profoundly abnormal ciliary movement at 37°C (Video 1) reverted to a more normally coordinated beat pattern with a greater range of movement at room temperature (Video 2), suggesting a PCD variant with temperature-dependent CBP. We conclude that cooling of cilia to allow diagnostic interrogation of ciliary function, in the absence of temperature controlled high-speed video microscopy equipment, may be inappropriate for the diagnostic screening of nasal epithelium for PCD.

Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.

Other contributions: Informed consent was provided by the parents of this case for use of clinical information and samples for academic research for “A study of the pathophysiology and clinical manifestations of PCD and other chronic respiratory disease of childhood” (LREC 06/Q1702/109).

Additional information: The videos can be found in the “Supplemental Materials” area of the online article.

Smith CM, Hirst RA, Bankart MJ, et al. Cooling of cilia allows functional analysis of the beat pattern for diagnostic testing. Chest. 2011;140(1):186-190.
 
Mwimbi XK, Muimo R, Green MW, Mehta A. Making human nasal cilia beat in the cold: a real time assay for cell signalling. Cell Signal. 2003;15(4):395-402.
 
Clary-Meinesz CF, Cosson J, Huitorel P, Blaive B. Temperature effect on the ciliary beat frequency of human nasal and tracheal ciliated cells. Biol Cell. 1992;76(3):335-338.
 
Kennedy JR, Duckett KE. The study of ciliary frequencies with an optical spectrum analysis system. Exp Cell Res. 1981;135(1):147-156.
 
Lucas JS, Adam EC, Goggin PM, et al. Static respiratory cilia associated with mutations in Dnahc11/DNAH11: a mouse model of PCD. Hum Mutat. 2012;33(3):495-503.
 
Knowles MR, Leigh MW, Carson JL, et al;. for the Genetic Disorders of Mucociliary Clearance Consortium for the Genetic Disorders of Mucociliary Clearance Consortium. Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure. Thorax. 2012;67(5):433-441.
 

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References

Smith CM, Hirst RA, Bankart MJ, et al. Cooling of cilia allows functional analysis of the beat pattern for diagnostic testing. Chest. 2011;140(1):186-190.
 
Mwimbi XK, Muimo R, Green MW, Mehta A. Making human nasal cilia beat in the cold: a real time assay for cell signalling. Cell Signal. 2003;15(4):395-402.
 
Clary-Meinesz CF, Cosson J, Huitorel P, Blaive B. Temperature effect on the ciliary beat frequency of human nasal and tracheal ciliated cells. Biol Cell. 1992;76(3):335-338.
 
Kennedy JR, Duckett KE. The study of ciliary frequencies with an optical spectrum analysis system. Exp Cell Res. 1981;135(1):147-156.
 
Lucas JS, Adam EC, Goggin PM, et al. Static respiratory cilia associated with mutations in Dnahc11/DNAH11: a mouse model of PCD. Hum Mutat. 2012;33(3):495-503.
 
Knowles MR, Leigh MW, Carson JL, et al;. for the Genetic Disorders of Mucociliary Clearance Consortium for the Genetic Disorders of Mucociliary Clearance Consortium. Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure. Thorax. 2012;67(5):433-441.
 
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